Tuberculosis Patients’ Serum Extracellular Vesicles Induce Relevant Immune Responses for Initial Defense Against BCG in Mice

Extracellular vesicles (EVs) can be distributed in various bodily fluids, such as serum and urine, and play an essential role in immune regulation, substance transport, and other aspects. Tuberculosis (TB) is an infectious disease caused by <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), which places a tremendous burden on public health prevention and control within society. Researchers are committed to developing various diagnoses and treatment plans to eliminate TB effectively. The results of some studies conducted to date demonstrate that the serum EVs of TB patients, which carry components related to <i>Mtb</i>, can be used as relevant markers for TB detection and improve diagnostic efficiency. However, no relevant reports exist on the particular physiological functions such EVs perform, thus warranting further exploration. In this study, we collected serum EVs from both healthy individuals and TB patients. After identifying the morphology, concentration, and expression of classic markers (CD63, CD81, and CD9) of EVs, we explored their physiological functions at the cellular level and their physiological functions and effects on BCG colonization in the lungs at the mouse level. It was found that EVs were abundant in TB patients and healthy individuals, and the number of CD63 and CD9 markers co-expressed on the surface of serum EVs in healthy individuals was greater than that in TB patients. Serum EVs in patients with TB can stimulate cells to secrete more immune cytokines, such as TNF-α and IL-6, compared with those in healthy individuals; induce an increase in the M1/M2 ratio of macrophages in the peripheral blood mononuclear cells of mice; and inhibit the colonization of <i>Mycobacterium bovis bacillus Calmette Guérin</i> (BCG) in the lungs of mice. In addition, they can inhibit the occurrence of inflammatory responses in the lung tissue of mice. The above results suggest that serum EVs in TB patients may exert their physiological function by regulating immune responses. This finding also indicates that exploring serum EVs in TB patients with regard to their physiological functions shows excellent potential.